SYMPOSIUM
The growing threat of antimicrobial resistance
BY JOSE M. MUNITA, MD; SAMUEL SHELBURNE, MD; DAVID E. GREENBERG, MD; AND CESAR A. ARIAS, MD
The emergence and widespread dis- semination of multidrug-resistant or- ganisms is considered one of the three most important public health threats for humankind in the 21st century and jeopardizes the practice of modern medicine. Failure to tackle this prob- lem in a comprehensive fashion could result in a dire post-antibiotic era, impairing the future development of treatments against important diseases, such as cancer, and transplant medi- cine, among others. Here, we provide a global perspective of the problem and describe some of the most important antibiotic-resistant organisms affect- ing the health of our patients. In ad- dition, we discuss some of the ongoing efforts to deal with the antimicrobial resistance crisis.
A MAJOR PUBLIC HEALTH THREAT
The discovery of antimicrobials is one of the most important milestones in the history of modern medicine. The antibiotic era led to a revolution in medicine, as antimicrobials became lifesaving drugs any clinician could access and provide to patients. The availability of antimicrobials became critical for the development of com- plex medical interventions such as cutting-edge surgical procedures, solid organ transplantation, manage- ment of patients with cancer, and ad- vanced intensive care support for the critically ill, among others. After billions of years, microbes
have developed an immense capacity to evolve, allowing them to adapt and withstand harmful conditions. These impressive and evolving skills of natu- ral selection have also provided them with the ability to develop different
48 TEXAS MEDICINE February 2017
mechanisms to survive in the pres- ence of antimicrobials. In fact, ev- ery new antimicrobial molecule that has been commercialized in clinical medicine has been followed shortly by reports of resistance. (See Figure 1.) Such bacterial genomic plasticity, coupled with the selective pressure resulting from massive antibiotic use, has led to rising rates of antimicrobi- al-resistant organisms. In clinical terms, antibiotic-resis-
tant bacteria have been categorized in three important groups: multidrug- resistant, which involves organisms that exhibit resistance to more than three families of antibiotics; extreme- ly drug-resistant, defined as organ- isms in which two or fewer antimi- crobials remain active in vitro; and pan-resistant, which refers to bacte- ria resistant to all clinically available antimicrobials (against which there are no therapeutic alternatives).1
The
emergence of the latter two groups of pathogenic bacteria has become a ma- jor public health threat that virtually returns us to the pre-antibiotic era. Indeed, in a recent survey of infec- tious disease specialists in the United States, 60 percent of responders in- dicated they had dealt with at least one pan-resistant bacterial infection within the previous year.2
As could
be expected, the increasing frequency of such strains jeopardizes modern medical achievements and may in- fluence the health of many patients around the world. Infections caused by multidrug-re-
sistant organisms are associated with increased mortality compared with those caused by susceptible bacteria, and they carry an important econom-
ic burden, estimated at more than $20 billion per year in the United States.3 The Centers for Disease Control
and Prevention (CDC) conservative- ly estimates at least 23,000 people die annually in the United States as a result of an infection caused by an antibiotic-resistant organism. More- over, according to a recent report from the United Kingdom, antibiotic resistance will cause about 300 mil- lion premature deaths by 2050, with a loss of up to $100 trillion to the global economy.4 To complicate things, there is a paucity of a robust antibiotic pipeline, with a steep decline in the number of new antibiotics approved in the Unit- ed States over the last decades. The World Health Organization designat- ed the antimicrobial resistance crisis as one of the three most important public health threats of the 21st cen- tury.5
The same organization warned
failure to address this crisis would re- sult in a catastrophic post-antibiotic era. The alarm of antimicrobial resis- tance has long been raised by the In- fectious Diseases Society of America6 and has now been recognized as a top priority by governments and funding agencies around the world. Impor- tant efforts to increase the funding of high-quality research in this area are ongoing. Several U.S. initiatives have been
developed at the highest level of gov- ernment to address the crisis. The Na- tional Strategy to Combat Antibiotic Resistance and the Interagency Task Force on Antimicrobial Resistance are high-level initiatives focused on com- bating the antibiotic-resistance threat. The Obama administration
nearly
doubled the federal funding to com- bat antimicrobial resistance to more than $1.2 billion in 2016. Following this move, CDC announced the release of $67 million to health departments nationwide to improve detection and identification of antibiotic-resistant bacteria, with emphasis in the local health departments of six major met- ropolitan areas, including Houston.
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